0

1

Workshop: Measuring the impact of pharmacovigilance activities 5-6 December 2016

Challenges and opportunities to measuring the impact of regulatory

actions

Sabine Straus Medicines Evaluation Board

The Netherlands

2

3

Regulatory actions

• PSUR

• Additional risk minimistation

4

CIOMS VIII The ultimate test for pharmacovigilance systems is the demonstration of public health benefit

ADR PSUR RMP PASS Questionnaires Additional RMM Referral Additional monitoring list Safety communications …….

5

Periodic Safety Update Reports

• Process indicators evidence that the implementing steps of risk minimisation measures have been successful

• Outcome indicators provide an overall measure of the level of risk control that has been achieved with a risk minimisation measure

6

performance of the overall program individual tool performance

RMM effectiveness: what to measure?

7

Communications

8

Communications

9

Communications

Challenges for DHPC

• Safety issue is identified and requires urgent action – Actionable recommendations – Target groups

• Definition of succes/failure

– What is succes

• Data – When – What – How

Communications

10

RMM effectiveness • Process indicators

– Implementation logistics/coverage/distribution • Distribution plan, target group, quality of the content

– Awareness and clinical knowledge • % of HCP or patients with sufficient knowledge regarding the risk

and ways to minimise it – Behavorial change/clinical action

• Impact on daily practice, adherence to guidance, impact on patients

• Outcome indicators

– Measure directly the health outcome goal – Surrogate endpoints if necessary

11

Risk minimisation

Pregnancy prevention programme (PPP) • a set of interventions aiming to minimise the risk on drug exposure

during pregnancy because of the drugs’ potential teratogenic effects – Do not start treatment in pregnant women – Do not become pregnant during treatment ( for a certain period of

after stopping)

12

Additional risk minimisation: PPP

• First version of the PPP in 1988 • In EU, in 2003 the PPP requirements for isotretinoine were

harmonised throughout EU with a referral procedure • All stakeholders are involved

– Prescriber – Pharmacist – Patient – Payer

Isotretinoin PPP

Measuring effectiveness of the PPP

• Decide on what to assess

• What is the objective of the PPP – No exposed pregnancies – No babies with birth defects – Full compliance to the recommended contraceptive

use – Full understanding of the teratogenic risk

13

14

15 BMJ Open 2014, IM Zomerdijk et al

Additional risk minimisation: PPP

• Spontaneous adverse event data potentially biased outcome measure systematic data collection or active surveillance of adverse events in populations with well-defined exposure • Active surveillance/data collection/sentinel sites costly, time consuming and may not detect rare events. issues relating to response rates, representativeness, and reporting biases may limit the accuracy of survey results. • Surveys not be the most appropriate approach for the evaluation of behaviour Well designed minimise potential biases and to optimise the generalizability • “The need for speed” existing databases, drug utilization studies

16

Challenges: datasources

Challenges: datasources Recycling existing data

• Limited recall bias • Wide scope and coverage • Longitudinal data • Rapidly available data • Low costs • Limitations databases

Active data collection

• Very specific data can be collected

• Slow • Low response rate • Bias (non)response • Cross-sectional • Costly • Self reported behaviour

17

• Definitions of success/failure: – What do we want to achieve, how should we measure eg

PPP?

In pregnancy prevention programs : No pregnancies No children with congenital abnormalities 100% use of contraception in combination with

teratogenic 100% awareness of the risks in HCP and users

18

Challenges: outcome definitions

• Definitions of success/failure: – What do we want to achieve , how should we measure eg PPP

• Quality of the aRMM

– A RMM should have a clearly defined objective/actionable /measurable in a timely way

Challenges: outcome definitions

19

• Definitions of success/failure: – What do we want to achieve , how should we measure eg PPP

• Quality of the aRMM

– A RMM should have a clearly defined objective/actionable

• Distinguishing between evaluation of goals and tools achievement of goals and performance of tools may not be linked

• Distinguishing between process and outcome – a need for different remedies

• Is more always better?

– Eg iPledge, is there an optimum?

20

Challenges……..

21

• Definitions of success/failure: – What do we want to achieve , how should we measure eg PPP

• Quality of the aRMM – A RMM should have a clearly defined objective

• Distinguishing between evaluation of goals and tools – achievement of goals and performance of tools may not be linked

• Distinguishing between process and outcome – If the RM does not perform need for different remedies

• Is more always better? – Eg iPledge, is there an optimum? – How to remedy if effectiveness seems to fail ?

• How to ensure speedy amendments if needed, based on good

quality data

22

Challenges: Need for speed

Summary of key issues

• Quality of (a)RMM

• Definitions of failure and success

• Readily available data versus customised data collection

Avoiding risks is impossible, managing them adequately is the key to success

23